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Targeted Suppression of Lipoprotein Receptor LSR in Astrocytes Leads to Olfactory and Memory Deficits in Mice

El Hajj, Aseel, Herzine, Ameziane, Calcagno, Gaetano, Désor, Frédéric, Djelti, Fathia, Bombail, Vincent, Denis, Isabelle, Oster, Thierry, Malaplate, Catherine, Vigier, Maxime, Kaminski, Sandra, Pauron, Lynn, Corbier, Catherine, Yen, Frances T., Lanhers, Marie-Claire, Claudepierre, Thomas·2022·International Journal of Molecular Sciences
DOI 10.3390/ijms23042049PMC PMC8878779
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Abstract

Perturbations of cholesterol metabolism have been linked to neurodegenerative diseases. Glia–neuron crosstalk is essential to achieve a tight regulation of brain cholesterol trafficking. Adequate cholesterol supply from glia via apolipoprotein E-containing lipoproteins ensures neuronal development and function. The lipolysis-stimulated lipoprotein receptor (LSR), plays an important role in brain cholesterol homeostasis. Aged heterozygote Lsr+/− mice show altered brain cholesterol distribution and increased susceptibility to amyloid stress. Since LSR expression is higher in astroglia as compared to neurons, we sought to determine if astroglial LSR deficiency could lead to cognitive defects similar to those of Alzheimer’s disease (AD). Cre recombinase was activated in adult Glast-CreERT/lsrfl/fl mice by tamoxifen to induce astroglial Lsr deletion. Behavioral phenotyping of young and old astroglial Lsr KO animals revealed hyperactivity during the nocturnal period, deficits in olfactory function affecting social memory and causing possible apathy, as well as visual memory and short-term working memory problems, and deficits similar to those reported in neurodegenerative diseases, such as AD. Furthermore, GFAP staining revealed astroglial activation in the olfactory bulb. Therefore, astroglial LSR is important for working, spatial, and social memory related to sensory input, and represents a novel pathway for the study of brain aging and neurodegeneration.

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Metadata

Authors
El Hajj, A., Herzine, A., Calcagno, G., Désor, F., Djelti, F., Bombail, V., Denis, I., Oster, T., Malaplate, C., Vigier, M., Kaminski, S., Pauron, L., Corbier, C., Yen, F. T., Lanhers, M.-C., & Claudepierre, T.
Affiliations
  • UR AFPA Laboratory, Qualivie Team, University of Lorraine, 54505 Vandoeuvre-lès-Nancy, France
  • UR 7300, Stress Immunity Pathogens Laboratory, Faculty of Medicine, University of Lorraine, 54500 Vandœuvre-lès-Nancy, France
  • UMR 914, Physiology of Nutrition and Feeding Behaviour, INRAE-Agroparistech-Université Paris-Saclay, 78352 Jouy-en-Josas, France
ORCID
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2022-02-12
Volume
23
Issue
4
Pages
2049
ISSN
1422-0067
DOI
10.3390/ijms23042049
PMC
PMC8878779
Cited by
9
References
7
Language
en
Licence
creativecommons.org/licenses/by/4.0/ (vor)
Funders
  • Region Lorraine (N/A)
  • FEDER (N/A)
  • Fondation Alzheimer (N/A)
  • LUE Impact Biomolecules (N/A)
  • Ministry of Higher Education Research and Innovation (N/A)
  • Inserm (N/A)

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